This invention relates to multiwell trays or titre plates used as containers for chemical or biochemical reactions, such as for polymerase chain reaction (PCR) and more particularly, to a rigid frame for holding a plastic PCR plate planar.
Molecular biological reactions are often carried out in trays, or titre plates, containing an array of wells. The polymerase chain reaction (PCR) is one such reaction. In it, tiny quantities of materials are processed through a long sequence of steps, including being heated with a heater block. Multiwell trays increase throughput by allowing many reactions to be performed at one time.
PCR has become such a routine procedure that cutting the cost of the apparatus by even small increments is important. Wells can be machined out of a rigid slab of material to form a multiwell plate, but injection molding has been found to produce a somewhat acceptable, and cheaper, plate. U.S. Des. Pat. No. D420,743 (Monks) is exemplary of plastic injection-molded trays.
The various liquid reactants can be individually inserted into each well by a hand-operated micropipettor. Typically, though, an automated dispenser performs this repetitive operation. Salomon et al. disclose (U.S. Pat. No. 4,478,094) such a dispenser. The Salomon apparatus has a row of dispensing tips that fill an entire row of wells on a tray. Other liquid dispensers have tips arranged in a matrix, which may be large enough to fill all the wells on a tray with one dispense cycle.
Ganged dispensers require that the trays have consistent dimensions and be planar. The longitudinal axes of the wells must be paraller to the direction of travel of the dispenser head, otherwise the dispensing tips may miss one or more of the wells, or jam against the walls of some of the wells such that the tray is picked up by the tips as the dispensing head retracts. This causes a xe2x80x9ccrashxe2x80x9d of the dispenser, which must be reset by the operator and may result in loss of the samples contained in a tray.
Although multiwell trays molded from polyethylene or polypropylene are superior in some ways, they are likely to have residual internal stresses from the molding operation. These stresses often cause warping of the tray immediately after ejection from the mold, or may cause delayed warping or dimensional change after thermal cycling of the tray. As a result of warping of the trays, the trays"" handling features for automated handling have large variations in their positions. This causes problems for automated handling equipment. In some applications, trays are stacked such that the positioning variations are compounded and the problems are greater.
Therefore, there is a need for a means for causing multiwell trays, injection molded from flexible plastic, to have the desirable qualities of rigid trays. Such a means preferably would hold the top surface of the tray planar, reduce dimensional variation of the tray, and not interfere with use of the tray.
The present invention is a rigid frame for holding a multiwell tray planar on top. By holding the tray top planar, the wells are kept parallel to each other so that a gang dispenser can be used without crashes.
In an exemplary embodiment, the multiwell tray has a rectangular tray top with wells suspended from it, a side wall projecting downward, and a flange around the base of the side wall forming a base that the tray stands on. There are apertures spaced around the side wall. The frame for holding this tray is a rectangular frame of a rigid material with low thermal expansion.
The frame has barbs spaced around its interior. When the frame is placed over the tray and pressed downward relative to the tray, the barbs snap into the apertures to retain the tray securely in the frame. Because the frame is attached at points around the perimeter of the tray, it holds the tray top planar, causing the long axes of the wells to be parallel, and perpendicular to the plane of the tray top. The frame adds weight to the tray, thus keeping it from being tipped or knocked over.
The frame remains on the tray throughout whatever processing the materials in the wells are undergoing. In the case of PCR, particularly, the process may include several thermal excursions. The frame constrains the tray from warping and keeps the outside dimensions of the tray/frame combination fairly constant. The frame includes features, such as machined indentations, that allow the frame to be manipulated by automated handlers. One aspect of the invention is that the tray can be installed in the frame in only one orientation. Index marks on the exterior of the frame indicate the orientation and can be used to allow automated handling in only one orientation, making it easier to keep track of well contents.